The object of the proposed research is to better understand the mechanism of menopausal hot flashes by simultaneously studying the associated thermoregulatory physiology and endocrinology. One basic question is whether hot flashes result from an alteration of a central thermoregulatory mechanism (i.e., a change in either "set point" or "gain"), or from a peripheral event which causes a series of responses in the presence of an unaltered thermoregulatory mechanism. To answer this question several approaches will be used. (1) Thermoregulatory function in non-flashing vs flashing intervals - Physiological changes will be monitored in subjects during and between hot flashes while in warm, neutral and cold ambient temperatures. Figer blood flow, heart rate, O2 consumption, CO2 production, skin and internal temperatures will be recorded. Metabolic and sweating rates during flashing and non-flashing intervals will be plotted against skin and internal temperature and fitted to equations, allowing an equation of the changes brought about by hot flashes. The relative contribution of central and peripheral temperatures to hot flash responses will also be examined by independently varying peripheral and core temperatures in paraplegic menopausal women. Hyoscine (scopolamine) iontophoresis into forehead or cheat skin will be used to assess the mechanism of flash-associated sweating. (2) Hormonal changes during hot flashes - Several circulating hormones and neuropeptides will be quantitated at warm, neutral and cold ambient temperatures to establish the temporal relationships between levels of these substances and hot flashes. (3) Induction of hot flashes - Stimuli of several modalities (e.g., thermal, gustatory, auditory, olfactory and tactile) will be administered in an attempt to elicit hot flashes. The physiological responses of induced vs "spontaneous" flashes will be compared. Menopausal hot flashes provide a unique opportunity to elucidate some aspects of the mechanism of thermoregulatory function in humans. These periodic flash episodes also pose a public health problem of considerable magnitude, affecting millions of women each year. It is felt that the information provided by this research will aid in our understanding of the mechanism of hot flashes and lead to new modes of therapy.